Phospholipid scramblase 4 (PLSCR4)

Phospholipid scramblase 4 (PLSCR4) is an enzyme that catalyzes the rapid, ATP-independent, bidirectional translocation (scrambling) of phospholipids between the inner and outer leaflets of the plasma membrane in response to increased intracellular calcium levels[6][1][4]. PLSCR4 is highly expressed in adipose tissue and structurally related to other members of the phospholipid scramblase family; it is predominantly localized at the plasma membrane[2][1]. Functionally, PLSCR4 regulates adipogenesis by modulating PI3K/AKT signaling through effects on PIP3, mediating important roles in cell membrane remodeling and signal transduction[2]. In disease, altered PLSCR4 expression has been linked to adipose tissue overgrowth (such as PTEN-associated lipomas) and increased in inflammatory lung disease (ARDS) models[2][3]. It also participates in mechanisms that protect against pyroptosis, a form of programmed cell death, by facilitating phosphatidylserine externalization and modulating gasdermin D–mediated pore formation[3]. There are currently no well-established pharmacological drugs directly targeting PLSCR4, and its broad physiological role suggests that therapeutic modulation would require careful assessment of downstream effects.

Other names

GIG43TRA1Ca(2+)-dependent phospholipid scramblase 4Cell growth-inhibiting gene 43 proteinCell growth inhibiting protein 43PL scramblase 4

Lipid scrambling (facilitating rapid, ATP-independent redistribution of phospholipids between membrane leaflets); Modulation of PI3K/AKT pathway through regulation of PIP3 levels; Inhibition of pyroptosis by enhancing phosphatidylserine translocation and potentially interfering with GSDMD pore formation